This application is a revised submission for a 5-year competitive continuation to grant 1R01-DA015269, Gender Identity and HIV Risk. The long-range goal of our research is to reduce HIV transmission among individuals stigmatized for their gender nonconformity and diversity, a goal consistent with the Healthy People 2010 objective to reduce the nation's health disparities. Key findings from our prior work were: a) a national sample of these individuals can be effectively reached via the Internet;b) differences in sex, gender identity/role, and sexual orientation are associated with important differences in HIV risk behavior;c) individuals in the female role are particularly vulnerable to HIV infection through the high risk behavior of the men with whom they interact. We propose to build on these findings by investigating the HIV risk behavior and cofactors of this population's high risk male partners (N=400), using online survey and interview methods successfully applied in the original project (Aim 1). These results will help inform the development of a theory- driven, Internet-based, HIV prevention intervention for individuals who are stigmatized for their gender non- conformity (Aim 2). The intervention will be modeled on an offline HIV intervention shown, in an uncontrolled trial, to reduce risk behavior in the target population. After user-testing and refinement of the prototype online intervention, we will conduct a randomized controlled trial (N=600) to evaluate its efficacy in improving health and reducing HIV risk behavior (Aim 3). This study is innovative in that a) few interventions exist for this minority population and even fewer have been adequately evaluated;b) the intervention will combine HIV prevention and behavior change theories with principles of e-learning;c) the entire study will be implemented online. Our team is highly experienced in HIV prevention research with diverse and vulnerable populations, the benefits/challenges of Internet-based research (online recruitment, data collection, intervention adaptation), and sexual health theory and measures. The project has public health significance in that the minority population targeted for intervention is at high risk for HIV infection, and the men with whom they interact not only pose a risk to them, but also to the general population. If proven effective, the online intervention can be implemented with little additional cost to reduce gender-related HIV risks on a large scale, nationally and internationally, even among highly stigmatized groups.